Biology Reference
In-Depth Information
Clinical Trials
DNA vaccines encoding antigens from pathogens and tumors have been
tested in early phase human trials. The initial studies were focused on
demonstrating the safety of this new class of vaccine. Although older,
widely utilized vaccines in some cases contained bacterial DNA
(for example, the earlier version of the pertussis vaccine, which was
made of killed pertussis), the use of recombinant DNA — although
highly purified with a known sequence of the DNA — required exten-
sive pre-clinical safety testing as well as the usual phase I clinical safety
studies. In various studies for diseases ranging from HIV and influenza
to the parasite malaria, the clinical trials generally demonstrated weak
but real immune responses, both antibodies and cellular immune
responses.
22,23
The low level of the responses was disappointing given
the ease with which potent immunity had been demonstrated in such
a large number of animal models. Yet certain interesting observations
have emerged. For example, certain HIV patients who had had long
exposures to high levels of viral antigens (due to their high viral loads),
yet who had not made cytolytic T cell responses against a particular
viral antigen, mounted cytolytic T cell responses against epitopes of
that protein following the DNA immunization.
22-24
Thus, by some
mechanism, the DNA resulted in the generation of immune responses
not evoked by the virus. This provided evidence that different meth-
ods of immunization (if infection with the virus to induce immune
responses may be called immunization) can have different outcomes
in terms of immune responses.
New Generation DNA Vaccines
Efforts have focused on ways to increase the potency of DNA vaccines.
One early and continuing approach has been to redesign the plasmids
to enable them to produce more protein antigen.
25,26
As data from
early clinical trials demonstrated the safety of administering DNA
vaccines to humans, increased doses of DNA have been used in clini-
cal trials, increasing to as much as 1-8 milligram doses per vaccine.
27,28
Other efforts have been directed at formulating the DNA in order to
